Target 5000: a standardized all-Ireland pathway for the diagnosis and management of inherited retinal degenerations
Citation:
Stephenson, K.A.J. and Zhu, J. and Wynne, N. and Dockery, A. and Cairns, R.M. and Duignan, E. and Whelan, L. and Malone, C.P. and Dempsey, H. and Collins, K. and Routledge, S. and Pandey, R. and Crossan, E. and Turner, J. and Oâ Byrne, J.J. and Brady, L. and Silvestri, G. and Kenna, P.F. and Farrar, G.J. and Keegan, D.J., Target 5000: a standardized all-Ireland pathway for the diagnosis and management of inherited retinal degenerations, Orphanet Journal of Rare Diseases, 2021, 16, 1Download Item:
s13023-021-01841-1.pdf (Published (author's copy) - Peer Reviewed) 1.235Mb
Abstract:
Introduction: Inherited retinal degenerations (IRD) are rare genetic disorders with > 300 known genetic loci, mani-
festing variably progressive visual dysfunction. IRDs were historically underserved due to lack of effective interven-
tions. Many novel therapies will require accurate diagnosis (phenotype and genotype), thus an efficient and effective
pathway for assessment and management is required.
Methods: Using surveys of existing practice patterns and advice from international experts, an all-Ireland IRD service
(Target 5000) was designed. Detailed phenotyping was followed by next generation genetic sequencing in both a
research and accredited laboratory. Unresolved pedigrees underwent further studies (whole gene/whole exome/
whole genome sequencing). Novel variants were interrogated for pathogenicity (cascade screening, in silico analysis,
functional studies). A multidisciplinary team (MDT; ophthalmologists, physicians, geneticists, genetic counsellors)
reconciled phenotype with genotype. A bespoke care plan was created for each patient comprising supports, existing
interventions, and novel therapies/clinical trials.
Results and discussion: Prior to Target 5000, a significant cohort of patients were not engaged with healthcare/sup-
port services due to lack of effective interventions. Pathogenic or likely pathogenic variants in IRD-associated genes
were detected in 62.3%, with 11.6% having variants of unknown significance. The genotyping arm of Target 5000
allowed a 42.73% cost saving over independent testing, plus the value of MDT expertise/processing. Partial funding
has transferred from charitable sources to government resources.
Conclusion: Target 5000 demonstrates efficacious and efficient clinical/genetic diagnosis, while discovering novel
IRD-implicated genes/variants and investigating mechanisms of disease and avenues of intervention. This model
could be used to develop similar IRD programmes in small/medium-sized nations.
Sponsor
Grant Number
Science Foundation Ireland (SFI)
Author's Homepage:
http://people.tcd.ie/gjfarrar
Author: Farrar, Gwyneth
Type of material:
Journal ArticleCollections:
Series/Report no:
Orphanet Journal of Rare Diseases;16;
1;
Availability:
Full text availableKeywords:
Public and patient involvement, Clinical diagnostic algorithm, Inherited retinal degenerations, Retinal dystrophy, Ocular genetics, Genetic diagnosisDOI:
http://dx.doi.org/10.1186/s13023-021-01841-1Licences: